Dental cement compositions and methods of use

ABSTRACT

Provided herein are dental compositions and methods for use in dental cementation applications.

RELATED APPLICATIONS

This application is a Continuation application of U.S. patentapplication Ser. No. 15/944,680 filed on Apr. 3, 2018, now U.S. Pat. No.10,751,263, issued on Apr. 25, 2020, which in turn claims the benefit ofU.S. Provisional Application No. 62/481,005, filed on Apr. 3, 2017, andthe contents of the aforementioned application are incorporated hereinby reference in their entirety.

FIELD OF THE INVENTION

The field of use is dental compositions, particularly those useful indental cementation applications.

BACKGROUND OF THE INVENTION

A dental restoration or dental filling is a dental restorative materialused to restore the function, integrity and morphology of missing toothstructure. The structural loss typically results from caries or externaltrauma (collectively referred to herein as cavities). It is also lostintentionally during tooth preparation to improve the aesthetics or thephysical integrity of the intended restorative material.

Dental cements are used for a variety of dental and orthodonticapplications, including use as luting agents, pulp-protecting agents orcavity-lining material. Furthermore, they are used to form an insulatinglayer under metallic, resin or ceramic restorations, and protect thepulp from injury. This helps in sealing or fixing and casting inlays,onlays, or any such substance to both dentin and enamel.

Resin cements usually have two categories: total-etch and self-adhesiveresin cements. For proper use, pure resin cements require pretreatmentof the tooth surface, preferably with phosphoric acid and application ofa dentin and enamel primer prior to application of the resin cement.After curing this forms a micromechanical bond to both dentin andenamel. Also, they are insoluble in oral fluids. There are 2 types ofthese “traditional resin cements” (those that require the use of the“total-etch technique and dentin adhesive technology”) that are commonlyused—dual-cured and light-cured versions. The most recent addition tothe “resin cement family” are the self-adhering resin cements thatrequire no pretreatment of the tooth surface and appear to have many ofthe clinical advantages of traditional resin cement systems, with theease of use of more traditional types of cements. It is important tonote that, in general, bond strengths of self-etching resin cements arenot as high as those for resin cements using the total-etch techniqueand, as a result, may more likely lead to microleakage at the margin.

An ideal dental cementation material may provide strong and durablecementation and ease of use.

SUMMARY OF THE INVENTION

Provided herein, in certain embodiments, are dental compositionscomprising a polymerizable monomer, and a hydroperoxide and/or thiourea.In some embodiments, the compositions further comprise copper (II)(e.g., as a catalyst).

Also provided herein is a dental composition, wherein said compositioncomprises, on a surface of a dental substrate, a bonding agent; and apaste mixture, wherein the bonding agent comprises at least onephosphoric acid containing (meth)acrylic monomer, wherein the pastemixture at least one polymerizable monomer, at least one hydroperoxide;and at least one thiourea compound. The phosphoric acid containing(meth)acrylic monomer is selected from the group consisting of GPDM(glycerol phosphate di(meth)acrylate{(meth)acrylate=acrylate ormethacrylate}), phenyl-P (phenyl methacryloxyethyl phosphate), PENTA-P(dipentaerithritol pentaacrylate phosphate), 10-MDP(methacryloyloxydecyl phosphate), HEMA-P (hydroxyethylmethacrylatephosphate), HEA-P (hydroxyethylacrylate phosphate), bis(HEMA)-P{bis(hydroxyethylmethacrylate) phosphate), bis(HEA)-P{bis(hydroxyethylacrylate) phosphate),bis((meth)acryloxypropyl)phosphate, and combinations thereof. In aparticular embodiment, the phosphoric acid containing (meth)acrylicmonomer is 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP). Thethiourea is selected from the group consisting of1-(2-Pyridyl)-2-thiourea (PTU), 1-Benzoyl-2-thiourea (BTU),1-Acetyl-2-thiourea (ATU), 1-(2-Tetrahydrofurfuryl)-2-thiourea (TTU), ora combination thereof. In a particular embodiment, the thiourea is1-(2-Pyridyl)-2-thiourea (PTU). In particular embodiments, thehydroperoxide is a tertiary hydroperoxide. In particular embodiments,either the first part or second part of the paste mixture furthercomprises a copper (II) compound. In a particular embodiment, the dentalsubstrate is Zirconia. In another embodiment, the bonding agent is asingle bottle bonding agent.

Also provided herein, is a method of dental restoration, wherein saidmethod comprises: a first step of applying a dental bonding agent on adental substrate, wherein the bonding agent comprises at least onephosphoric acid containing (meth)acrylic monomer; and a second step ofapplying paste mixture from a device having a first part and a secondpart separate from each other, wherein said first part and second partform the past mixture, and wherein the paste mixture from the devicecomprises at least one polymerizable monomer and at least onehydroperoxide in the first part; and at least on thiourea compound inthe second part. In particular embodiments, the phosphoric acidcontaining (meth)acrylic monomer is selected from the group consistingof GPDM (glycerol phosphate di(meth)acrylate{(meth)acrylate=acrylate ormethacrylate}), phenyl-P (phenyl methacryloxyethyl phosphate), PENTA-P(dipentaerithritol pentaacrylate phosphate), 10-MDP(methacryloyloxydecyl phosphate), HEMA-P (hydroxyethylmethacrylatephosphate), HEA-P (hydroxyethylacrylate phosphate), bis(HEMA)-P{bis(hydroxyethylmethacrylate) phosphate), bis(HEA)-P{bis(hydroxyethylacrylate) phosphate),bis((meth)acryloxypropyl)phosphate, and combinations thereof. In aparticular embodiment, the phosphoric acid containing (meth)acrylicmonomer is 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP). Thethiourea is selected from the group consisting of1-(2-Pyridyl)-2-thiourea (PTU), 1-Benzoyl-2-thiourea (BTU),1-Acetyl-2-thiourea (ATU), 1-(2-Tetrahydrofurfuryl)-2-thiourea (TTU), ora combination thereof. In a particular embodiment, the thiourea is1-(2-Pyridyl)-2-thiourea (PTU). In particular embodiments, thehydroperoxide is a tertiary hydroperoxide. In particular embodiments,either the first part or second part of the paste mixture furthercomprises a copper (II) compound. The bonding agent bonds effectively ona dental substrate. In a particular embodiment, the dental substrate isZirconia. In particular embodiments, the bond strength of the dentalbonding agent on a dental substrate is more than 15 MPa. In oneembodiment, the device is a dual-barrel syringe.

Also provided is a dental composition, wherein said compositioncomprises, on a surface of a dental substrate, a bonding agent; and apaste mixture, wherein the bonding agent comprises at least onephosphoric acid containing (meth)acrylic monomer, wherein the pastemixture was formed by mixing together a previously separated first partand a second part, and wherein the first part comprises at least onepolymerizable monomer and at least one hydroperoxide; and the secondpart comprises at least one thiourea compound. In a particularembodiment, the previously separated first part and a second part wereseparated in a dual-barrel syringe.

In other embodiments the dental composition comprises a first part and asecond part, the first part comprising: a copper (II) catalyst; ahydroperoxide; and a polymerizable monomer, the polymerizable monomercomprising an ethylenic group, and the second part comprising: a copper(II) catalyst; a thiourea; and a polymerizable monomer, thepolymerizable monomer comprising an ethylenic group. In specificembodiments, the first and second parts are physically separated (e.g.,until such a time as the dental composition is used to restore a cavityin a tooth).

In some embodiments, provided herein is a dental composition comprisinga first and a second part, the first and second part collectivelycomprising: a copper (II) catalyst; a hydroperoxide; a polymerizablemonomer, the polymerizable monomer comprising an ethylenic group; and athiourea. In specific embodiments, the first part comprises the hydrogenperoxide, the second part comprises the thiourea, and the first and thesecond part are physically separated from each other (e.g., until such atime as the dental composition is used to restore a cavity in a tooth).

In some embodiments, provided herein is a dental composition, a partthereof, or a resin precursor thereof, wherein said compositioncomprises: a copper (II) catalyst; a hydroperoxide; and a polymerizablemonomer (e.g., the polymerizable monomer comprising an ethylenic group).Similarly, in certain embodiments, provided herein is a dentalcomposition, a part thereof, or a resin precursor thereof, wherein saidcomposition comprises: a copper (II) catalyst; a thiourea; and apolymerizable monomer (e.g., the polymerizable monomer comprising anethylenic group).

In some embodiments, provided herein is a dental composition (e.g., afast curing, copper free, acid free composition) comprising a first anda second part, the first and second part collectively comprising: ahydroperoxide (e.g., the hydroperoxide being a tertiary arylhydroperoxide (e.g., HOOCR′₃, wherein each R′ is independently alkyl oraryl, with at least one R′ being aryl (e.g., substituted orunsubstituted aryl), such as cumenehydroperoxide); a polymerizablemonomer (e.g., the polymerizable monomer comprising an ethylenic group);and a thiourea. In some embodiments, the first part comprises thehydrogen peroxide, the second part comprises the thiourea, and the firstand the second parts are physically separated from each other. Inspecific embodiments, the hydroperoxide has a concentration in thedental composition of about 1.5% (w/w) or more or a concentrationrelative to the monomer of about 1.5% (w/w) or more. In more specificembodiments, the hydroperoxide has a concentration in the dentalcomposition of about 2% (w/w) or more or a concentration relative to themonomer of about 2% (w/w) or more. In still specific embodiments, thehydroperoxide has a concentration in the dental composition of about2.5% (w/w) or more or a concentration relative to the monomer of about2.5% (w/w) or more. In further or alternative embodiments, the thioureahas a concentration in the dental composition of about 1.5% (w/w) ormore or a concentration relative to the monomer of about 1.5% (w/w) ormore. In more specific embodiments, the thiourea has a concentration inthe dental composition of about 2% (w/w) or more or a concentrationrelative to the monomer of about 2% (w/w) or more. In still specificembodiments, the thiourea has a concentration in the dental compositionof about 2.5% (w/w) or more or a concentration relative to the monomerof about 2.5% (w/w) or more. In further or additional embodiments, thecombined weight of the hydroperoxide plus thiourea has a concentrationin the dental composition of about 3% (w/w) or more or a concentrationrelative to the monomer of about 3% (w/w) or more. In more specificembodiments, the combined weight of the hydroperoxide plus thiourea hasa concentration in the dental composition of about 4% (w/w) or more or aconcentration relative to the monomer of about 4% (w/w) or more. Instill specific embodiments, the combined weight of the hydroperoxideplus thiourea has a concentration in the dental composition of about 5%(w/w) or more or a concentration relative to the monomer of about 5%(w/w) or more.

In certain embodiments, the copper (II) catalyst comprises a copper (II)ion and/or a copper (II) compound. In specific embodiments, the copper(II) catalyst comprises copper (II) sulfate, copper (II) acetate, copper(II) chloride, copper (II) acetylacetonate, or a combination thereof. Insome embodiments, the copper (II) catalyst is present in the compositionin an amount of about 5 wt. % or less (e.g., about 1 wt % or less, orabout 0.1 wt. % or less).

In some embodiments, the hydroperoxide comprises a hydrocarbon (e.g.,C₄-C₂₀ hydrocarbon) substituted with one or more —OOH group. In specificembodiments, the hydroperoxide is a tertiary hydroperoxide (e.g., the—OOH group is substituted with a carbon having tertiary substitution).In more specific embodiments, the hydroperoxide is or comprises t-butylhydroperoxide, t-amyl hydroperoxide, p-diisopropylbenzenehydroperoxide,cumenehydroperoxide, pinanehydroperoxide, p-menthanehydroperoxide, and1,1,3,3-tetramethylbutyl hydroperoxide, or a combination thereof. Infurther or alternative embodiments, the hydroperoxide is present in thecomposition in an amount of about 0.01% (w/w) to about 10% (w/w). Inmore specific embodiments, the hydroperoxide is present in thecomposition in an amount of about 0.1% (w/w) to about 5% (w/w). In someembodiments, the hydroperoxide is present in the composition in a ratioof hydroperoxide to polymerizable monomer of about 1:9999 to about 1:9.In more specific embodiments, the ratio of hydroperoxide topolymerizable monomer is about 1:99 to about 5:95.

In certain embodiments, the monomer is a dentally acceptable monomer. Insome embodiments, the monomer comprises a vinyl, an acrylate, amethacrylate, or a combination thereof. In further or alternativeembodiments, the monomer is present in an amount of about 10% (w/w) toabout 60% (w/w). In more specific embodiments, the polymerizable monomeris present in an amount of about 20% (w/w) to about 50% (w/w).

In certain embodiments, the thiourea comprises 1-(2-Pyridyl)-2-thiourea(PTU), 1-Benzoyl-2-thiourea (BTU), 1-Acetyl-2-thiourea (ATU),1-(2-Tetrahydrofurfuryl)-2-thiourea (TTU), or a combination thereof. Infurther or alternative embodiments, the thiourea is present in thecomposition in a ratio of thiourea to polymerizable monomer of about1:999 to about 100:900. In more specific embodiments, the ratio ofthiourea to polymerizable monomer is about 1:99 to about 10:90.

In specific embodiments, a dental composition provided herein comprisesa filler. In more specific embodiments, the first and second partscomprise a filler. In still more specific embodiments, the filler is afinely divided filler. In some embodiments, the finely divided fillercomprises a plurality of particles. In specific embodiments, theparticles having an average dimension (e.g., diameter) of about 0.02microns to about 30 microns, e.g., about 0.2 microns to about 10microns. In further or alternative embodiments, the filler comprises aninorganic filler, a pre-polymerized filler, or a combination thereof.Fillers include, by way of non-limiting example, metal oxide, a metalnitride, a metal fluoride, a silicate, silica (e.g., colloidal silica,precipitated silica, fused silica), an aluminosilicate, analuminoborosilicate, a fluoroaluminosilicate, a bariumsilicate, abariumaluminosilicate, a barium aluminoborosilicate, astrontiumaluminosilicate, a bariumfluoroaluminosilicate, astrontiumfluoroaluminosilicate, a strontiumzincfluoroaluminosilicate, azinc aluminosilicate, a pre-polymerized filler, and a combinationthereof. In some embodiments, the filler is present in an amount ofabout 10% (w/w) to about 90% (w/w). In more specific embodiments, thefiller is present in an amount of about 40% (w/w) to about 80% (w/w). Instill more specific embodiments, the filler is present in an amount ofabout 60% (w/w) to about 80% (w/w).

In some embodiments, the composition comprises a photoinitiator, astabilizer, a solvent, or any combination thereof. In some embodiments,a photoinitiator is present in an amount of about 5% (w/w) or less. Infurther or alternative embodiments, a stabilizer is present in an amountof about 1% (w/w) or less.

In some embodiments, a composition provided herein is free of, orsubstantially free of, an acid or anhydride. In specific embodiments,the composition (and/or part(s) thereof) comprises less than 5% (w/w) ofan acid (e.g., less than 3% (w/w), less than 1% (w/w), or less than 0.5%(w/w)). In particular embodiments, the composition, or parts thereof, isnon-acidic (e.g., having a pH of about 5 or more).

In various embodiments, compositions provided herein have goodperformance characteristics, such as when utilized in restorative dentalapplications (e.g., in restoring a tooth with a Class I or Class IIcavity). In specific embodiments, upon combination of the first andsecond parts, the total volume of the composition shrinks by less than10% (e.g., less than 8%, less than 6%, or less than 4%)(e.g., as itsets). In some instances, minimizing such shrinkage reduces theincidences of void formation between a filling and a tooth, reducesincidences of damage (e.g., cracking) to the tooth during and followingrestoration, and the like. In further or alternative embodiments, uponcombination of the first and second parts, the hygroscopicity of thecomposite is less than 100 μg/mm³ (e.g., less than 50 μg/mm³, less than25 μg/mm³, less than 20 μg/mm³, or less than 15 μg/mm³). In someinstances, minimizing the hygroscopicity reduces expansion of therestoration material following curing to a resultant composite which, inturn, may reduce incidences of damage (e.g., cracking) to the tooth,dislodgement of the filling from the tooth, and/or the like.

Also provided herein are dental composites resulting from the mixing ofcomposition components or parts described herein, e.g., partially orwholly cured mixtures. In some embodiments, the composite comprises apartially or wholly cured resin, filler and copper. In specificembodiments, the composite comprises the cured resin in an amount ofabout 10% (w/w) to about 60% (w/w), the filler in an amount of about 10%(w/w) to about 90% (w/w), and the copper in an amount of about 1elemental wt. % or less. Also provided herein is a reaction mixturecomprising a copper (II) catalyst; a hydroperoxide; a polymerizablemonomer, the polymerizable monomer comprising an ethylenic group; and athiourea. The reaction mixture may be partially cured, with a portion ofthe monomeric units thereof forming monomers and other portions formingoligomer or polymers thereof.

In some embodiments, two part compositions provided herein are containedwithin a dual chambered device comprising a housing body, the housingbody comprising a first chamber and a second chamber, the first chambercontaining the first part of a composition described herein, the secondchamber containing the second part of a composition described herein. Inspecific embodiments, dual chambered device is configured toconcomitantly extrude and/or mix the first and second parts.

Also provided herein is a method for restoring a tooth in an individual.In some embodiments, the process comprises combining a first composition(e.g., a first part of a dental composition described herein) with asecond composition (e.g., a second part of a dental compositiondescribed herein) to form a mixed composition. In specific embodiments,the first composition comprising a hydroperoxide, the second compositioncomprising a thiourea, and one or both of the first and/or secondcompositions comprising a copper (II) catalyst, a polymerizable monomer(e.g., the polymerizable monomer comprising an ethylene group), and afiller. In some embodiments, the method further comprises administeringthe mixed composition to an individual (e.g., to a Class I or Class IIcavity in a tooth of the individual). In some embodiments, the processfurther comprises curing the mixed composition (e.g., allowing thecomposition to self-cure, and/or using a dental curing light tophoto-cure the composition). In specific embodiments, curing of themixed composition results in the formation of a restoration composite(e.g., in the form of a filling within a dental cavity of theindividual). In preferred embodiments, the curing step (e.g.,self-curing) occurs relatively quickly in order to facilitate therestoration process. In specific embodiments, the curing step (e.g.,self-curing or setting) occurs within 10 minutes, within 4 minutes,within 2 minutes, or the like.

In a particular embodiment, the invention method comprises the stepsof: 1) applying a dental bonding primer on dentin and enamel (e.g., thetooth structure), optionally followed by a curing activator, optionallycuring the primer layer with a dental curing light; 2) applying a dentalbonding primer on prefabricated restorations, such as crowns, inlays,onlays, veneers, optionally followed by a curing activator, optionallycuring the primer layer with a dental curing light; 3) applying a dentalcement layer to bond prefabricated restorations to the tooth structure(dentin and enamel).

In some embodiments, the method comprises removing decay from in andaround a cavity to be filled (e.g., drilling the tooth to remove decaytherefrom).

These and other objects, features, and characteristics of thecompositions, parts thereof, precursors thereof, resultant composites,and methods disclosed herein, as well as the methods of manufacture,will become more apparent upon consideration of the followingdescription and the appended claims with reference to the accompanyingdrawings, all of which form a part of this specification. It is to beexpressly understood, however, that the drawings are for the purpose ofillustration and description only and are not intended as a definitionof the limits of the invention. As used in the specification and in theclaims, the singular form of “a”, “an”, and “the” include pluralreferents unless the context clearly dictates otherwise.

DETAILED DESCRIPTION OF THE INVENTION

Provided herein are dental compositions. Also provided herein arecomponent parts thereof, dental restoration processes, resins used inthe preparation of dental compositions, dental composites (e.g., fillingmaterials), and the like. In specific embodiments, the dentalcompositions comprise two parts, such as two parts that are keptphysically separated from each other. In some instances, when the twoparts are combined, such as when the dental composition is used in adental restoration process (such as described herein), the compositionforms a composite (e.g., a filling material used in tooth restoration).

In particular embodiments, provided herein is a dental compositioncomprising two parts (e.g., with free radical polymerization beinginitiated upon the mixing thereof), the two part dental compositioncomprising, in some embodiments:(1) at least one monomer with at leastone ethylenically unsaturated group (e.g., also referred to herein as apolymerizable monomer comprising an ethylenic group, such as describedherein); (2) one part comprising at least one hydroperoxide group; and(3) one part comprising at least one substituted thiourea. In morespecific embodiments, the two part dental composition comprises:(1) atleast one monomer with at least one ethylenically unsaturated group; (2)one part comprising at least one hydroperoxide group; (3) one partcomprising at least one substituted thiourea; (4) at least one partcomprising at least one copper (II) compound (e.g., a copper (II)compound that catalyzes, such as, facilitates and/or speeds up curing ofthe composition (e.g., polymerization of the monomeric componentsthereof) upon combination of the first and second parts).

In specific embodiments, provided herein is a dental compositioncomprising a first and a second part, the first part comprising: (1) acopper (II) catalyst; (2) a hydroperoxide; and (3) a polymerizablemonomer comprising an ethylenic group, and the second part comprising:(1) a copper (II) catalyst; (2) a thiourea; and (3) a polymerizablemonomer comprising an ethylenic group. Also provided herein are theindividual first and second parts thereof, including, e.g., a dentalcomposition comprising (1) a copper (II) catalyst; (2) a hydroperoxide;and (3) a polymerizable monomer comprising an ethylenic group, and/or adental composition comprising (1) a copper (II) catalyst; (2) athiourea; and (3) a polymerizable monomer comprising an ethylenic group.

In certain embodiments, provided herein is a dual chambered devicecomprising a housing body, the housing body comprising a first chamberand a second chamber, the first chamber containing therein the firstpart of a composition described herein, and the second chambercontaining therein the second part of a composition provided herein. Insome embodiments, the dual chambered device is any suitable devicesuitable for concomitantly extruding the first and second parts, such asto allow the mixing of the first and second parts and facilitateinitiation and polymerization of the monomeric component(s) thereof. Inspecific embodiments, the dual chambered device is a dual barreledsyringe comprising a nozzle configured to facilitate mixing of the firstand second parts upon (concurrent) depression of a comprising a firstand second plunger.

In certain embodiments, the monomer with at least one ethylenicallyunsaturated group or polymerizable monomer comprising an ethylenic groupis a compound comprising at least one >C═C< group. In specificembodiments, the monomer is represented by the formula R₂C═CR₂, whereineach R is independently selected from H, COOR¹, or an optionallysubstituted hydrocarbon, such as alkyl, aryl, or the like, such aswherein at least one R is not H. In specific embodiments, at least one Ris COOR¹ or an aryl (e.g., phenyl, or the like). In some embodiments, R¹is either H or alkyl (e.g., C₁-C₆ alkyl). In more specific embodiments,the alkyl is a C₁-C₆ alkyl (e.g., methyl, ethyl, or the like). Incertain embodiments, an alkyl is an acyclic (e.g., branched or straightchain) or cyclic, saturated or unsaturated alkyl. In some embodiments,optional substituents include, by way of non-limiting example, —OH,alkyl, and/or aryl. In certain embodiments, the monomer comprises one ormore moiety represented by the formula R₂C═CRL, wherein the R and Lgroups are independently as described for the R groups above. In certainembodiments, a monomer comprises two or more R₂C═CRL groups, wherein theL groups are linked together (e.g., as R₂C═CRL—(LCR═CR₂)_(a), whereina>0, such as 1-5, e.g., 1-2), such as illustrated in Formula I:

For example, in some embodiments, the monomer is optionallyR₂C═CR—COO((CH₂)_(m)(CHOH)_(n))_(p)OOC—RC═CR₂, wherein m is 1-6 (e.g.,2-4), n is 0-1, and p is 1-30 (e.g., 1-10).

In specific embodiments, the monomer is an acrylate (e.g., wherein threeR groups=H and one R group=COOR¹), a methacrylate (e.g., wherein two Rgroups=H, one R group=methyl, and another R group (on the same carbon asthe methyl) is COOR¹), or a vinyl group (wherein at least one R group isa hydrocarbon). In some embodiments, the monomer comprises an acrylate,a methacrylate, and/or a vinyl group. In specific embodiments, theethylenically unsaturated group is selected from acrylate andmethacrylate groups. Examples of polymerizable monomers include, but arenot limited to, the following: glycerol di(meth)acrylate, glycerolmono(meth)acrylate, hydroxyethyl (meth)acrylate {(meth)acrylate=acrylateor methacrylate}, hydroxypropyl (meth)acrylate, methyl (meth)acrylate,ethyl (meth)acrylate, propyl (meth)acrylate, octyl (meth)acrylate, decyl(meth)acrylate, 2-ethoxyethyl (meth)acrylate, 2′-ethoxy-2-ethoxyethyl(meth)acrylate, ethyleneglycol di(meth)acrylate, diethyleneglycoldi(meth)acrylate, triethyleneglycol di(meth)acrylate; polyethyleneglycolmono-(meth)acrylate, polyethyleneglycol di-(meth)acrylate,polypropyleneglycol mono-(meth)acrylate, polypropyleneglycoldi-(meth)acrylate, polytetramethyleneglycol mono-(meth)acrylate,polytetramethyleneglycol di-(meth)acrylate, hexanediol di(meth)acrylate,octanediol di(meth)acrylate, decanediol di(meth)acrylate,trimethyloylpropane tri(meth)acrylate, urethane dimethacrylate (reactionadduct of 2-hydroxyethyl methacrylate with 2,4,4-trimethylhexanediisocyanate),2,2-bis[4-(2-hydroxy-3-methacryloylpropoxy)-phenyl]-propane (Bis-GMA),ethoxylatedbisphenol A dimethacrylate (where total number of moles ofethylene oxide in the molecule may range from 2 to 30 units) intetrahydrofurfuryl (meth)acrylate, or mixtures thereof. As referred toherein, “(meth)acrylate” includes disclosures of both methacrylate andacrylate.

In certain embodiments, the amount of monomer present in the compositionis any suitable amount. In certain embodiments, a dental compositionprovided herein comprises monomer in a weight percentage (e.g., of thetotal composition) amount between 10% and 60%. In more specificembodiments, the weight percentage is between 20% and 50%.

In certain embodiments, compositions provided herein comprise copper(II), such as in the form of a copper (II) compound. In specificinstances, copper(II) (e.g., a copper (II) compound) is utilized tocatalyze curing (e.g., hardening, or otherwise setting) of thecomposition (e.g., accelerate or otherwise facilitate polymerization ofthe monomer). In specific instances, the presence of the copper (II)(e.g., compound thereof) accelerates the polymerization process when twoparts of the inventive composition are mixed (e.g., whereby separatedhydroperoxide and thiourea come together and facilitate initiation ofpolymerization, which is accelerated by the presence of the copper(II)). A copper (II) catalyst is optionally in a disassociated,associated (e.g., in the form of a copper (II) compound), or partiallyassociated form. In various embodiments, the copper (II) compound is anysuitable compound that comprises at least one copper (II) in itsmolecular formula. Examples of copper (II) compounds include, but arenot limited to, copper (II) sulfate, copper (II) acetate, copper(II)chloride, copper (II) acetylacetonate, and combinations thereof. Inspecific embodiments, the copper (II) compound is copper (II) acetate.In other embodiments, the said copper (II) compound is copper (II)acetylacetonate. In specific embodiments, the weight percentage of thecopper (II) (or compound thereof) is less than 1%. In more specificembodiments, the weight percentage of the copper (II) (or compoundthereof) is less than 0.1%. In still more specific embodiments, thecopper (II) (or compound thereof) is provided in, or combined in, acomposition herein in an amount of about 0.001 wt. % to about 0.05 wt %.

In certain embodiments, the hydroperoxide is any suitable agent,particularly a dentally acceptable agent, such as that when combinedwith a thiourea provided herein initiates and/or otherwise facilitatespolymerization of the monomer herein, such as at a rate suitable fordental applications, particularly restorative applications. In someembodiments, the hydroperoxide is represented by the formula HOO—R²,wherein R² is any suitable organic group. In specific embodiments, R² isa hydrocarbon, such as a C₄-C₂₀ hydrocarbon (optionally substituted withany suitable groups, such as alkyl groups, aryl groups (e.g., phenyl),alkylaryl groups, additional —OOH groups, and/or the like). In someembodiments, R² is represented by the formula: —CR³R⁴R⁵, wherein each ofR³, R⁴, and R⁵ are independently H, alkyl (cyclic and/or acyclic, andbranched or straight chain), aryl (e.g., phenyl), arylalkyl (e.g.,attached to the carbon at the alkyl), alkylarylalkyl, or the like,wherein such groups are optionally substituted or unsubstituted. In someembodiments, at least two of R³, R⁴, and R⁵ are not H. In specificembodiments, the hydroperoxide is a tertiary hydroperoxide, i.e.,wherein none of R³, R⁴, and R⁵are H. In certain instances, any one ormore of R³, R⁴, and/or R⁵ are optionally taken together with another orboth of R³, R⁴, and R⁵ to form a cyclic (mono or polycyclic) alkyl group(which is optionally substituted or unsubstituted, such as discussedherein). As discussed herein, any suitable hydroperoxide compound withat least one hydroperoxide group is optionally used. In specificembodiments, the hydroperoxide compound comprises more than onehydroperoxide group. Non-limiting examples of hydroperoxide compoundsinclude, but are not limited to, t-butyl hydroperoxide, t-amylhydroperoxide, p-diisopropylbenzenehydroperoxide, cumenehydroperoxide,pinanehydroperoxide, p-methane hydroperoxide, and1,1,3,3-tetramethylbutyl hydroperoxide.

In some embodiments, any suitable concentration of hydroperoxide isoptionally utilized in the compositions and methods provided herein. Inspecific embodiments, the total hydroperoxide compound(s) is in therange of about 0.01% (w/w) to about 10.0% (w/w) (e.g., of the overallcomposition). In certain embodiments, the hydroperoxide is present inthe range of about 0.1% (w/w) to about 5.0% (w/w) of the overallcomposition. In some embodiments, the hydroperoxide is present in thecomposition in an amount of about 1.5% (w/w) to about 5% (w/w). Incertain instances, hydroperoxides provided herein, such as amongst thosedescribed above, are stable under a variety of conditions and have along shelf-life.

Any suitable thiourea is optionally utilized in a compositions describedherein (e.g., in at least one part of a two-part composition describedherein). In some embodiments, the thiourea is a substituted thiourea,such as a dentally acceptable thiourea. In some embodiments, thethiourea is an organic thiourea, e.g., a thiourea substituted with anorganic radical (e.g., a pyridyl, acetyl, or the like). In specificembodiments, the thiourea is represented by the structureR⁶R⁷NC(═S)NR⁸R⁹, wherein R⁶, R⁷, R⁸, and R⁹ are independently selectedfrom H, COR¹⁰, heterocycloalkyl and heteroaryl (e.g., theheterocycloalkyl or heteroaryl being substituted or unsubstituted), R¹⁰being an alkyl, heteroalkyl(cyclic or acylic), aryl, or heteroaryl (R¹⁰being substituted or unsubstituted). In specific embodiments, thethiourea group is attached to the heterocycloalkyl or heteroaryl at acarbon alpha to a heteroatom of the ring. In some embodiments, at leastone of or one of R⁶, R⁷, R⁸, and R⁹ is not H. In specific embodiments,the substituted thiourea is selected from the group consisting of1-(2-Pyridyl)-2-thiourea (PTU), 1-Benzoyl-2-thiourea (BTU),1-Acetyl-2-thiourea (ATU), 1-(2-Tetrahydrofurfuryl)-2-thiourea (TTU) andany mixture thereof (i.e., any one or more of PTU, BTU, ATU, and/orTTU).

In certain embodiments, combination of the two parts of the compositionprovided herein results in curing of the composition. In specificinstances, combination of the two parts, particularly the hydroperoxideand the thiourea thereof, facilitates initiation of polymerization ofthe monomer component of the composition. In certain embodiments,inclusion of the copper (II) catalyst accelerates the curing process(e.g., polymerization of the monomer component(s)), resulting in a settime that is fast enough to be suitable for dental applications. In someinstances, when the two-parts are mixed, the mixed composition cures(e.g., sets or hardens). In one embodiment, the setting time is lessthan 20 minutes (e.g., without the need for photo-curing using aphoto-curing device emitting a majority of light having a wavelength inthe blue range (e.g., 400 nm to 530 nm, such as about 470 nm)). In oneembodiment, the setting time is less than 10 minutes. In one embodiment,the setting time is less than 5 minutes. In more preferred embodiments,the cure (e.g., set) time is about 250 seconds or less. In preferredembodiments, the cure (e.g., set) time is about 180 seconds or less. Infurther or alternative embodiments, the composition, when the two partsare combined, has a work time of about 200 seconds or less, e.g., about150 seconds or less. Further, in some embodiments, the work time is atleast 30 seconds (e.g., to allow restoration or filling of a toothcavity, particularly a Class I or Class II cavity).

In certain embodiments, additional additives are included in thecomposition and/or parts thereof. In some embodiments, any suitableadditive is optionally included, such as, by way of non-limitingexample, a photo-initiator, a filler, a stabilizer, a solvent, or acombination thereof. In specific embodiments, a dental composition (orpart thereof) comprises a resin composition and a filler (e.g., theresin composition comprising the materials of a dental compositiondescribed herein),In more specific embodiments, each part of acomposition provided herein comprises a resin composition (e.g., acomposition comprising monomer described herein) and filler.

In specific embodiments, a composition (or part thereof) provided hereincomprises a filler, e.g., at least one finely divided filler. In someinstances, a filler may reduce polarization shrinkage, improvemechanical properties and increase radiopacity of a dental composite. Infurther or alternative instances, a filler may change the rheologicalproperties of a dental composition. Exemplary fillers include, but arenot limited to, metal oxides, metal nitrides, metal fluorides, silicateglass, colloidal silica, precipitated silica, fused silica,aluminosilicate glass, aluminoborosilicate glass, fluoroaluminosilicateglass, bariumsilicate, bariumaluminosilicate, bariumaluminoborosilicate,strontiumaluminosilicate, bariumfluoroaluminosilicate,strontiumfluoroaluminosilicate, strontiumzincfluoroaluminosilicate,zincaluminosilicate pre-polymerized composite filler, and anycombination of one or more thereof. Examples of metal oxides andfluorides include, but are not limited to, barium oxide, strontiumfluoride, barium fluoride, ytterbium fluoride, yttrium fluoride, zincoxide, bismuth(III) oxide. In one embodiment, the said filler is treatedwith a coupling agent such as γ-methacryloyloxypropyltrimethoxysilane(MPTMS). In some instances, such treatment enhances the interfacialbonding between the filler and resin matrix, and improves mechanicalproperties.

In some embodiments, the filler is a finely divided filler, e.g., afiller comprising or comprised of a plurality of solid particles. Incertain embodiments, the finely divided filler (e.g., particles thereof)has any suitable average dimension, such as, for example, an averagesize (e.g., particle size) of between 0.02 micron (μall) and 30 micron.In specific embodiments, the average size is between 0.2 micron and 10micron.

In certain embodiments, the filler is present in a composition providedherein in any suitable amount. In some embodiments, the filler (e.g.,finely divided filler) is present in the composition in an amountbetween 10 wt. % and 90 wt. %. In specific embodiments, the weightpercentage is between 40% and 80%.

In certain embodiments, a composition (or part thereof) provided hereinfurther comprises at least one photo-initiator. Any suitablephoto-initiator(s) is optionally included. Examples of a photo-initiatorinclude, but are not limited to, benzoin and derivatives, 2,2-diethoxyacetophenone, camphoroquinone, 1-phenyl-1,2-propanedione,monoacylphosphine oxide, bisacylphosphine oxide, and a mixture thereof.Additionally, an activator can be used together with a photo-initiator.Examples of activators include, but are not limited to,2-ethyl-4-(N,N-dimethylamino) benzoate, 2-amyl-4-(N,N-dimethylamino)benzoate, 2-octyl-4-(N,N-dimethylamino) benzoate;2-(ethylhexyl)-4-(N,N-dimethylamino) benzoate, N,N-dimethylaminoethylmethacrylate, N,N-dimethylaminophenethyl alcohol and a mixture thereof.In one embodiment, the photo-initiator system comprises camphoroquinoneand a tertiary amine selected from the group of2-ethyl-4-(N,N-dimethylamino) benzoate, 2-amyl-4-(N,N-dimethylamino)benzoate, 2-octyl-4-(N,N-dimethylamino) benzoate;2-(ethylhexyl)-4-(N,N-dimethylamino) benzoate, N,N-dimethylaminoethylmethacrylate, N,N-dimethylaminophenethyl alcohol and any mixture of oneor more thereof. In one embodiment, the weight percentage of the photoinitiator is less than 5%. In one embodiment, the weight percentage ofthe photo initiator is less than 3%.

In certain embodiments, a composition provided herein comprises at leastone stabilizer. In some instances, a stabilizer is an agent thatinhibits polymerization, such as of the monomer component(s) of acomposition described herein. In certain instances, such agents areuseful for improving the shelf life of a composition provided herein(e.g., inhibiting polymerization of the monomer prior to use). Anysuitable stabilizer, or polymerization inhibiter (such as a free radicalscavenger), is optionally utilized herein. Stabilizers include, by wayof non-limiting example, 2,6-di-(tert-butyl)-4-methylphenol (BHT) and4-methoxyphenol (MEHQ). Any suitable amount of stabilizers is optionallyutilized, such as less than 1 wt. %.

In certain embodiments, provided herein are methods of utilizing andmanufacturing such compositions, such as in and for dental applications.In general instances, such compositions are prepared in a dentallyacceptable manner (i.e., in a manner suitable for administration intothe mouth (or tooth cavity thereof) of an individual, patient orperson). In specific embodiments, provided herein is a method ofadministering a composition described herein to an individual, such asto restore a tooth of the individual. In specific embodiments, acomposition described herein is provided, any parts thereof are combinedto form a mixed composition (e.g., wherein the monomers of thecompositions are being polymerized), administering the mixed compositionto the individual (e.g., into a cavity of the individual), and curingthe mixed composition (e.g., until set).

In specific embodiments, the method is utilized to restore a tooth(e.g., a tooth comprising a cavity). In some embodiments, thecomposition is administered to, delivered into, and/or used to restore atooth comprising a Class I or Class II cavity (e.g., based on the G.V.Black classification system), or a cavity in a posterior tooth. Incertain embodiments, a Class I cavity is a cavity located in a pit orfissure of the occlusal surfaces of molars and premolars, the occlusaltwo-thirds of the buccal surfaces of molars, the lingual surfaces ofupper incisors, or in the lingual surfaces of upper molars. In someembodiments, a Class II cavity is a cavity in the proximal surface of amolar or premolar. In certain embodiments, the composition isparticularly useful in providing an effective mechanism of filling largecavities—an area where other restoration compositions are lacking. Inspecific embodiments, a cavity treated according to a process herein hasa depth of about 3 mm or more (e.g., about 4 mm or more, about 5 mm ormore, about 5 mm to about 7 mm, or the like) from any surface of thetooth (e.g., the fill surface of the tooth, or where the surface of thetooth was prior to the cavity, or would have been in the absence of thecavity).

In some embodiments, the mixture is further cured by a dental curinglight, e.g., after it sets at the intraoral conditions. In further oralternative embodiments, an additional layer of a dental compositionprovided herein is placed on top of the set or cured mixture followed bycuring with a dental curing light.

In specific embodiments, the parts of a composition provided herein aremixed to form a mixed composition, the mixed composition beingadministered to an individual (e.g., a dental cavity of the individual),and the mixed composition being cured under ambient conditions (or,being allowed to self-cure) for up to 15 minutes (e.g., 0.2 minutes to15 minutes, 0.5 minutes to 10 minutes, 1 minutes to 6 minutes, 2 minutesto 5 minutes, or 3 minutes to 4 minutes, and the like). In specificinstances, curing under ambient conditions comprises allowing thecomposition to set (e.g., cure in the absence of a light initiatordevice, such as a device that emits light, a majority of which having ablue wavelength (e.g., in the 400-530 nm range, or about 470 nm)). Inspecific embodiments, the cured (e.g., self-cured or set) composite isfurther cured using a light initiator device, such as a device thatemits light, a majority of which having a blue wavelength (e.g., in the400-530 nm range, or about 470 nm). In more specific embodiments, priorto light curing, additional mixed composition is administered to thecavity. In some instances, light curing at the surface is desirable, tofacilitate complete curing of the filling at the surface (e.g., whereinradical—e.g., of living polymer and/or initiator—groups may interact anddie in the air prior to complete polymerization/curing).

In some embodiments, one or more of the desirable restorative materialcharacteristics described herein is achieved in any suitable manner,such as by using the concentrations of materials described herein. Incertain embodiments, provided herein is a composition (e.g., two partcomposition) comprising copper (II), such as described herein. In someembodiments, presence of the copper (II) catalyzes the curing (e.g.,self-curing) of a composition at a rate sufficient to be dentallyeffective. In some embodiments, the amount of copper (II) (or compoundthereof) present need not be much to have an effect. For example, insome embodiments, less than 0.1 wt. % or even less than 0.01 wt. % ofcopper (II) (or compound thereof) is utilized. In further or alternativeembodiments, good curing rates are achieved using higher concentrationsof hydroperoxide and/or thiourea. In some embodiments, a compositionprovided herein comprises a combined concentration of hydroperoxide andthiourea (e.g., the hydroperoxide and thiourea provided in separateparts of the composition) is about 2.5 wt. % (relative to the totalweight of the monomer—i.e., {{wt. hydroperoxide+wt. thiourea}/total wt.monomer}*100%) or more, about 3 wt. % or more, about 4 wt. % or more, orabout 5 wt. % or more.

Provided in certain embodiments herein is a dental cement comprising thecured combination of the first and second parts of any compositionherein, or the cured combination of any composition comprising thioureawith any composition comprising a hydroperoxide described herein. Incertain embodiments, one or both parts of a composition described hereincomprise a copper (II) catalyst. In some embodiments, a compositeprovided herein comprises a cured resin (e.g., comprising polymerizedmonomer(s) described herein), filler and copper. In specificembodiments, the composite comprises cured resin in any suitable amount,such as an amount described herein for a composition comprising amonomer (e.g., about 10 wt. % to about 60 wt. %), the filler in anysuitable amount, such as an amount described herein for a compositioncomprising the filler (e.g., about 10 wt. % to about 90 wt. %, and thecopper in an amount of about 1 elemental wt. % or less (e.g., based onamount of copper present on an elemental basis) (e.g., about 0.1 wt. %or less, about 0.05 wt. % or less, or the like). In specificembodiments, the dental composite comprises filler in an amount of about60% (w/w) to about 80% (w/w) and cured resin in an amount of about 20%(w/w) to about 40% (w/w).

In certain embodiments, the dental cement compositions provided and usedherein have no to low acid and/or anhydride content. In specificembodiments, the acid and/or anhydride content is less than 5 wt. % ofthe composition. In more specific embodiments, the acid and/or anhydridecontent is less than 3 wt. % of the composition, less than 2 wt. % ofthe composition, less than 1 wt. % of the composition, less than 0.5 wt.%, less than 0.1 wt. % of the composition, or the like. In someembodiments, the composition has a substantially neutral or alkalinenature, such as a pH of about 5 or higher, a pH of about 5.5 of higher,a pH of about 6 or higher, a pH of about 6.5 or higher, or a pH of about7 or higher. In specific instances, it is preferred that the acidcontent of the composition be minimized for any reason, such as tominimize hygroscopicity or water sorption of the resultant composite. Insome instances, high levels of water sorption into the composite, whenused as a restoration material, may result in volume expansion in therestoration material, which may lead to deformation of the restorationmaterial, and, ultimately, dislodgement of the restoration material,damage to the tooth, and/or other undesirable outcomes.

In certain embodiments, a composition provided herein cures to acomposite (or a composite provided herein has) a water sorption of about100 μg/mm³ or less. In specific embodiments, the water sorption is about50 μg/mm³ or less, about 25 μg/mm³ or less, about 20 μg/mm³ or less, orabout 15 μg/mm³.

In some embodiments, composites described herein (e.g., formed from thecombination of the composition parts described herein) have goodphysical parameters for dental applications. In some embodiments, suchcomposites have good flexural strength (e.g., greater than 50 MPa,greater than 100 MPa, greater than 125 MPa, or the like). In further oralternative embodiments, the composites have good compression strength(e.g., greater than 100 MPa, greater than 150 MPa, greater than 200 MPa,greater than 250 MPa, or the like). In certain embodiments, thecomposites have good diametral strength (e.g., greater than 30 MPa,greater than 40 MPa, greater than 45 MPa, or the like),In someembodiments, composites provided herein good water solubility (e.g.,less than 1 μg/mm³). In certain embodiments, the composites providedherein have good radiopacity (e.g., greater than 200% Al, greater than300% AI, or the like). Any suitable process is optionally utilized todetermine such parameters, such as testing a film comprising such acomposite (e.g., the film having a thickness of about 10 microns toabout 15 microns, such as about 14 microns).

Also provided herein are methods of manufacturing the compositionsdescribed herein. In some embodiments, the component parts of thecompositions described herein are combined in any suitable order.Exemplary processes are set forth in the Examples. In specificembodiments, a part of a composition provided herein is prepared bycombining monomer, hydroperoxide, optional stabilizer, and optionalphotoinitiator. In some embodiments, combination thereof is mixed toform a resin to which filler is added and blended or milled. Likewise, apart of a composition provided herein is, in specific embodiments,prepared by combining monomer, thiourea, optional stabilizer, andoptional photoinitiator. In some embodiments, combination thereof ismixed to form a resin to which filler is added and blended or milled.Exemplification of specific agents (as well as the correspondingcomponent class type) as set forth in the examples are to be understoodas being included in the disclosure of compositions and methodsdescribed herein.

A ceramic is an inorganic, non-metallic, solid material comprisingmetal, non-metalormetalloidatoms primarily held in ionic and covalentbonds. In dentistry, ceramic materials have been widely used tofabricate dental crowns and typical ceramic materials include, but notlimited to, zirconium oxide, feldspathic porcelain, lithiumdisilicate.In order to have good bonding strength on these materials, a primer maybe needed prior to cementation.

A pre-cured dental resin may also be used to fabricate dental crowns anda primer may also be needed to generate sufficient bond strength.

In some embodiments, the method comprises steps: 1) applying a dentalbonding primer on dentin and enamel, optionally followed by a curingactivator, optionally curing the primer layer with a dental curinglight; 2) applying a dental bonding primer on prefabricatedrestorations, such as crowns, inlays, onlays, veneers, optionallyfollowed by a curing activator, optionally curing the primer layer witha dental curing light; and 3) applying a dental cement layer to bondprefabricated restorations to the tooth structure (dentin and enamel).

In some embodiments, the dental bonding primer comprises at least onepolymerizable monomer with at least one phosphoric acid pendant group.In some embodiments, the monomer is selected from the group consistingof Ethylene glycol methacrylate phosphate, Bis [2-(methacryloyloxy)ethyl] phosphate, 10-Methacryloyloxydecyl dihydrogenphosphate, glycerolphosphate di(meth)acrylate, phenyl-P (phenyl methacryloxyethylphosphate), PENTA-P (dipentaerithritolpentaacrylate phosphate).

In some embodiments, the dental bonding primer comprises at least onepolymerizable monomer with at least one carboxylic acid or anhydridependant group. In some embodiments, the monomer is selected from thegroup consisting of (meth)acrylic acid, maleic anhydride, trimelliticanhydride, 4-META (4-methacryloxyethyltrimellitic anhydride), maleicanhydride, trimellitic anhydride, 4-META (4-methacryloxyethyltrimelliticanhydride); PM-HEMA (addition product of pyromellitic acid anhydride and2-hydroxyethyl methacrylate), PM-GDM (addition product of pyromelliticacid anhydride and glycerol dimethacrylate), BTDA-HEMA (addition productof 3,3′,4,4′-benzophenonetetracarboxylic dianhydride and hydroxyethylmethacrylate), and PA-HEMA (addition product of phthalic anhydride andhydroxyethyl methacrylate), MA-GDM (addition product of maleic anhydrideand glycerol dimethacrylate).

In some embodiments, the dental bonding primer comprises at least oneethylenically unsaturated group with at least one (meth)acrylate group.In specific embodiments, the ethylenically unsaturated group is selectedfrom acrylate and methacrylate groups. Examples of polymerizablemonomers include, but are not limited to, the following: glyceroldi(meth)acrylate, glycerol mono(meth)acrylate, hydroxyethyl(meth)acrylate {(meth)acrylate=acrylate or methacrylate}, hydroxypropyl(meth)acrylate, methyl (meth)acrylate, ethyl (meth)acrylate, propyl(meth)acrylate, octyl (meth)acrylate, decyl (meth)acrylate,2-ethoxyethyl (meth)acrylate, 2′-ethoxy-2-ethoxyethyl (meth)acrylate,ethyleneglycol di(meth)acrylate, diethyleneglycol di(meth)acrylate,triethyleneglycol di(meth)acrylate; polyethyleneglycolmono-(meth)acrylate, polyethyleneglycol di-(meth)acrylate,polypropyleneglycol mono-(meth)acrylate, polypropyleneglycoldi-(meth)acrylate, polytetramethyleneglycol mono-(meth)acrylate,polytetramethyleneglycol di-(meth)acrylate, hexanediol di(meth)acrylate,octanediol di(meth)acrylate, decanediol di(meth)acrylate,trimethyloylpropane tri(meth)acrylate, urethane dimethacrylate (reactionadduct of 2-hydroxyethyl methacrylate with 2,4,4-trimethylhexanediisocyanate),2,2-bis[4-(2-hydroxy-3-methacryloylpropoxy)-phenyl]-propane (Bis-GMA),ethoxylatedbisphenol A dimethacrylate (where total number of moles ofethylene oxide in the molecule may range from 2 to 30 units) intetrahydrofurfuryl (meth)acrylate, or mixtures thereof. As referred toherein, “(meth)acrylate” includes disclosures of both methacrylate andacrylate.

In some embodiments, the dental bonding primer comprises at least onesolvent. In some embodiments, the solvent is selected from the groupconsisting of ethanol, isopropanol, n-propanol, n-butanol, t-butanol,acetone, methyl ethyl ketone, water.

In some embodiments, the curing activator is a chemical that generatesfree radical at acidic environment.

In some embodiments, the material of the prefabricated restorations is apre-cured dental resin material with at least one inorganic filler. Insome embodiments, the material of the said prefabricated restorations isa ceramic. In some embodiments, the said ceramic is selected from thegroup consisting of zirconium oxide, feldspathic porcelain, lithiumdisilicate.

In some embodiments, the dental primer on prefabricated restorations isa dental bonding agent. In some embodiments, the dental primer is aprimer that comprises at least one silane with at least one(meth)acrylate pendant group.

In some embodiments, the dental cement is delivered through a dentaldual-barrel syringe equipped with a mixing tip onto the saidprefabricated restorations.

In some embodiments, the excess of the dental cement is cleaned with adental instrument. In some embodiments, the dental cement is optionallycured by a dental curing light.

In some instances, as used herein, a “set time” is the amount of timeunder which a mixed composition provided herein (i.e., a compositioncombining both parts of a two-part described composition describedherein) forms a solid or hard composite (which is partially orcompletely cured), particularly in the absence of an ancillary devicedesigned to facilitate the curing of restoration materials, such as adental curing light (e.g., also referred to herein as “self-curing”). Adental curing light is a piece of dental equipment that is used forpolymerization of light cure resin based composites. It can be used onseveral different dental materials that are curable by light. The lightused falls under the visible blue light spectrum. This light isdelivered over a range of wavelengths and varies for each type ofdevice. There are four basic types of dental curing lights; Tungstenhalogen, light-emitting diode (LED), plasma arc curing (PAC), and laser.In certain instances, the “work time” is the length of time after whichthe mixed composition ceases being malleable using typical dentaltechniques and/or equipment.

As used herein, weight percentage (wt. % or % (w/w)) refers, unlessotherwise noted, the percentage of the weight of a component relative tothe overall weight of a composition or composite. In some embodiments,the weight percentage refers to the weight of the component relative tothe weight of a two part composition (e.g., wherein a first and secondpart are physically separated) and/or the weight of the componentrelative to the weight of one part of a two part composition. In someinstances, the weight percentage of the component may be identical orsimilar in both parts of the two part system, and in other instances,the component may have different weight percentages in each part of thetwo part system. For example, in general instances, the hydroperoxideand thiourea each have different weight percentages in each of theparts, with the hydroperoxide being wholly or primarily in a first partof the composition and the thiourea being wholly or primarily in asecond part of the composition.

The term “alkyl” as used herein, alone or in combination, refers to anoptionally substituted straight-chain, or optionally substitutedbranched-chain saturated or unsaturated hydrocarbon monoradical having,e.g., from one to about ten carbon atoms, more preferably one to sixcarbon atoms. Examples include, but are not limited to methyl, ethyl,n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl,2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl,2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl,4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl,4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl,2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl,isopentyl, neopentyl, tert-amyl and hexyl, and longer alkyl groups, suchas heptyl, octyl and the like. Whenever it appears herein, a numericalrange such as “C₁-C₆ alkyl,” means that in some embodiments, the alkylgroup consists of 1 carbon atom; in some embodiments, 2 carbon atoms; insome embodiments, 3 carbon atoms; in some embodiments, 4 carbon atoms;in some embodiments, 5 carbon atoms; or, in some embodiments, 6 carbonatoms, although the present definition also covers the occurrence of theterm “alkyl” where no numerical range is designated. In addition, insome instances, such as wherein the alkyl is substituted on either side(e.g., as set forth for L above), the alkyl may refer to a diradicalderived from the above-defined monoradical, alkyl. Examples include, butare not limited to methylene (—CH₂—), ethylene (−CH₂CH₂—), propylene(—CH₂CH₂CH₂—), isopropylene (—CH(CH₃)CH₂—) and the like. An “alkyl” mayalso refer to a cyclic alkyl group, referring to an optionallysubstituted, saturated, hydrocarbon monoradical ring, containing, e.g.,from three to about fifteen ring carbon atoms or from three to about tenring carbon atoms, though, in some embodiments, includes additional,non-ring carbon atoms as substituents (e.g. methylcyclopropyl). The termincludes fused, non-fused, bridged and spiro radicals. In someembodiments, a fused cycloalkyl contains from two to four fused ringswhere the ring of attachment is a cycloalkyl ring. Examples include, butare not limited to cyclopropyl, cyclopentyl, cyclohexyl, cumene, andpinanering systems.

The term “aryl” as used herein, alone or in combination, refers to anoptionally substituted aromatic hydrocarbon radical of six to abouttwenty ring carbon atoms, and includes fused and non-fused aryl rings. Afused aryl ring radical contains from two to four fused rings where thering of attachment is an aryl ring, and the other individual rings arealicyclic, heterocyclic, aromatic, heteroaromatic or any combinationthereof. Further, the term aryl includes fused and non-fused ringscontaining from six to about twelve ring carbon atoms, as well as thosecontaining from six to about ten ring carbon atoms. A non-limitingexample of a single ring aryl group includes phenyl; a fused ring arylgroup includes naphthyl, phenanthrenyl, anthracenyl, azulenyl; and anon-fused bi-aryl group includes biphenyl.

The term “heteroaryl” as used herein, alone or in combination, refers tooptionally substituted aromatic monoradicals containing from about fiveto about twenty skeletal ring atoms, where one or more of the ring atomsis a heteroatom independently selected from among oxygen, nitrogen, andsulfur, but not limited to these atoms and with the proviso that thering of said group does not contain two adjacent O or S atoms. Inembodiments in which two or more heteroatoms are present in the ring,the two or more heteroatoms are the same as each another, or some or allof the two or more heteroatoms are different from the others. The termheteroaryl includes optionally substituted fused and non-fusedheteroaryl radicals having at least one heteroatom. The term heteroarylalso includes fused and non-fused heteroaryls having from five to abouttwelve skeletal ring atoms, as well as those having from five to aboutten skeletal ring atoms. In certain instances, bonding to a heteroarylgroup is via a carbon atom or a heteroatom. A non-limiting example of asingle ring heteroaryl group includes pyridyl or furanyl.

The term “heteroalkyl” as used herein, refers to optionally substitutedalkyl structure, as described above, in which one or more of theskeletal chain carbon atoms (and any associated hydrogen atoms, asappropriate) are each independently replaced with a heteroatom (i.e. anatom other than carbon, such as though not limited to oxygen, nitrogen,sulfur, or combinations thereof). Exemplary heteroalkyl groups includestraight chain groups, such as ethylene oxides (e.g., —CH2CH2On—), orringed groups, such as tetrahydrofuran.

EXAMPLES

Abbreviations for materials used in the examples include, as follows:

PTU: 1-(2-Pyridyl)-2-thiourea

CHP: Cumene hydroperoxide

CuPD: Copper(II) acetylacetonate

MDP: 10-Methacryloyloxydecyl dihydrogen phosphate

R202: AEROSIL® fumed silica

R812S: AEROSIL® fumed silica

GM27884-K6: Schott GM27884 Dental Glass, 3 μm

YbF3: Ytterbium Fluoride

BYK W9010: Wetting and dispersing additive (flow modifier)

CQ: Camphorquinone

EDMAB: Ethyl-4-dimethylamino benzoate

UDMA: Urethane dimethacrylate

E6BAD: Ethoxylated (6) Bisphenol A Dimethacrylate

EBPADM: Ethoxylated (3) Bisphenol A Dimethacrylate

BisGMA: Bisphenol A-glycidyl methacrylate

TEGDM: Triethylene glycol dimethacrylate

BHT: Butylatedhydroxytoluene

HDK N-20P: Fumed silica

Pluronic L-44: Surfactant

DI water: Distilled water

DHEPT: N-N-bis(2-hydroxyethyl)-P-toluidine

BPO: Benzoyl peroxide

Examples 1 Preparing a Bonding Agent having 16% MDP

Examples 1 and 2 were prepared by adding and mixing chemicals. Allchemicals were mixed until all solids, except fumed silica, weredissolved, resulting in low viscosity liquid.

Example 1 BisGMA 23.4 HEMA 15.6 EDMAB 0.7 CQ 0.5 BHT 0.04 HDK N-20P 3.6MDP 16 Pluronic L-44 0.1 DI Water 5 Ethanol 35 Total 99.94

Example 2 Preparing a Bonding Agent having 8% MDP and 8% PMDM

Example 2 was prepared by mixing Example 1 and 2 in proportions.

Example 2 BisGMA 23.4 HEMA 15.6 EDMAB 0.7 CQ 0.5 BHT 0.04 HDK N-20P 3.6MDP 8 PMDM 8 Pluronic L-44 0.1 DI Water 5 Ethanol 35 Total 99.94

Comparative Example A Preparing a Bonding Agent having 0% MDP and 16%PMDM

Examples 1 and 2 were prepared by adding and mixing chemicals. Allchemicals were mixed until all solids, except fumed silica, weredissolved, resulting in low viscosity liquid.

Comparative Example A BisGMA 23.4 HEMA 15.6 EDMAB 0.7 CQ 0.5 BHT 0.04HDK N-20P 3.6 PMDM 16 BYK W9010 0.1 DI Water 5 Ethanol 35 Total 99.94

Example 3 Preparing a First Part CHP-Coinitiator-Containing Paste

Example 3 was prepared by adding and mixing chemicals. Resin chemicalswere mixed together with dissolvable solids, including CQ, EDMAB andBHT, until all solids were dissolved. Solid fillers, including R812S,YbF3 and GM27884 were then added and mixed by a speed mixer and followedby a three-roll mill, resulting in a paste-like semi-solid.

Example 3 E6BAD 5.8 BISGMA 3.4 TEGDM 6.1 UDMA 2.6 EBPADM 10.3 EDMAB 0.06CQ 0.02 BYK-W 9010 0.1 BHT 0.03 CHP 0.6 R812S 1 YbF3 9 GM27884-K6 61Total 100.01

Example 4 Preparing a Second Part PTU-Coinitiator-Containing Paste

Example 4 was prepared by adding and mixing chemicals. Resin chemicalswere mixed together with dissolvable solids, including CQ, EDMAB, PTUand BHT, until all solids were dissolved. CuPD was added to a mixer ofTEGDMA and mixed by a speed mixer. Solid fillers, including R812S, YbF3,and GM27884 were then added and mixed by a speed mixer, followed by athree-roll mill, resulting in a paste-like semi-solid.

Example 4 E6BAD 5.6 BISGMA 3.4 TEGDM 5.9 UDMA 2.54 EBPADM 10 EDMAB 0.06CQ 0.025 BYK-W 9010 0.1 BHT 0.03 PTU 0.3 CuPd 0.0005 R202 0.01 YbF3 9R812S 1 GM27884-K6 62 Total 99.97

Example 5 Preparing Mixture of a First Part Example 3 Paste and a SecondPart Example 4 Paste

Example 5 was prepared by packing Examples 3(CHP-coinitiator-containing) and 4 (PTU-coinitiator-containing) into adual-barrel syringe, with each barrel hosting one respective paste as aFirst Part and Second Part. When this combination of pastes is used, amixing tip is attached so that both pastes can pass through a mixingchamber and have proper mixing. Upon mixing, the material will hardenover the time period of about 4 to 8 minutes.

Example 7 and 8 and Comparative Example B Application of Bonding Agentand Mixed First and Second Parts Cement Paste

Zirconia substrates were embedded into polymer resin and exposed bytrimming off the top layer. Substrates were exposed and polished with600 grit SiC paper. Zirconia surfaces were further sandblasted with 50nm aluminum oxide powders at a pressure of 60 psi. All specimens werethen thoroughly rinsed. A layer of bonding agent from either Example 1or 2 or Comparative Example A was applied with light brushing motion,followed by air thinning for about 10 seconds. The specimen was thenplaced into a bonding jig that is described in ISO 29022-2013. The pastemixture of Example 5 was injected into the cavity and kept in a 35° C.humidity chamber for one hour before it was taken off the jig. Thespecimen was then placed in water and kept at an oven at 37° C. for 20hours. The bond strength of the specimen was then recorded according toISO 29022-2013. With 10 specimens of each group, the average bondstrength and standard deviation are recorded in Table 1. The resultsindicate that the MDP containing bonding agents at either 16%(Example 1) or 8% (Example 2) provide bond strengths above 15 MPa at19.8 MPa and 19.1 MPa, respectively; whereas the bonding agent incomparative Example A lacking MDP has inferior bond strength below 15MPa at 11.6 MPa.

TABLE 1 Bond strength and standard deviations Example ExampleComparative 7 8 Example B Bonding agents Example 1 Example 2 ComparativeExample A Cement pastes Example 5 Example 5 Example 5 Bond strength(MPa) 19.8 19.1 11.6 Standard deviation 3.2 4.3 4.0

Comparative Example C Preparing a First Part BPO-Coinitiator-ContainingPaste

Comparative Example C was prepared by adding and mixing chemicals asdone in Example 3. Resin chemicals were mixed together with dissolvablesolids, including CQ, EDMAB, BPO and BHT, until all solids weredissolved. Solid fillers, including R812S, YbF3 and GM27884 were thenadded and mixed by a speed mixer, followed by a three-roll mill,resulting in a paste-like semi-solid.

Comparative Example C E6BAD 5.6 BISGMA 3.4 TEGDM 6.1 UDMA 2.6 EBPADM10.4 EDMAB 0.06 CQ 0.023 BYK-W 9010 0.15 BHT 0.03 BPO 0.6 R812S 1 YbF3 9GM27884-K6 61 Total 99.963

Comparative Example D Preparing a Second PartDHEPT-Coinitiator-Containing Paste

Comparative Example D was prepared by adding and mixing chemicals asdone in Example 4. Resin chemicals were mixed together with dissolvablesolids, including CQ, EDMAB, DHEPT and BHT, until all solids weredissolved. Solid fillers, including R812S, YbF3 and GM27884 were thenadded and mixed by a speed mixer, followed by a three-roll mill,resulting in a paste-like semi-solid.

Comparative Example D E6BAD 5.6 BISGMA 3.3 TEGDM 5.9 UDMA 2.5 EBPADM 10EDMAB 0.06 CQ 0.023 BYK-W9010 0.14 BHT 0.03 DHEPT 0.6 YbF3 9 R812S 1GM27884-K6 61.9 Total 100.053

Comparative Example E Preparing Mixture of a First Part Example C Pasteand a Second Part Example D Paste

Comparative Example E was prepared as done in Example 5 by packingComparative Examples C and D into a dual-barrel syringe, with eachbarrel hosting one paste. When this combination of pastes is used, amixing tip is attached so that both pastes can pass through a mixingchamber and have proper mixing. Upon mixing, the material will hardenover the time period of about 4 to 8 minutes.

Comparative Example F and G Application of Bonding Agent and Mixed Firstand Second Parts Cement Paste

As done in Examples 7 and 8, Zirconia substrates were embedded intopolymer resin and exposed by trimming off the top layer. Substrates wereexposed and polished with 600 grit SiC paper. Zirconia surfaces werefurther sandblasted with 50 nm aluminum oxide powders at a pressure of60 psi. All specimens were then thoroughly rinsed. A layer of Example 1or 2 was applied with light brushing motion, followed by air thinningfor about 10 seconds. The specimen was then placed into a bonding jigthat is described in ISO 29022-2013. The paste mixture of ComparativeExample E was injected into the cavity and kept in a 35° C. humiditychamber for one hour before it was taken of the jig. The specimen wasthen placed in water and kept at an oven at 37° C. for 20 hours. Thebond strength of the specimen was then recorded according to ISO29022-2013. With 10 specimens of each group, the average bond strengthand standard deviation are recorded in Table 2. The results shown inTable 2 indicate that when BPO (Example C) and DHEPT (Example D) areused as coinitiators in the First Part and Second Partcoinitiator-containing-paste for preparing the cement paste, the bondstrengths are much lower and weaker at 8.1 MPa and 11.4 MPa than whenCHP (Example 3) and PTU (Example 4) at 19.8 MPa and 19.1 MPa,respectively, are used as coinitiators in the First Part and SecondPart.

TABLE 2 Bond strength and standard deviations Comparative ComparativeExample F Example G Bonding agents Example 1 Example 2 Cement pastesComparative Comparative Example E Example E Bond strength 8.1 11.4Standard deviation 3.3 3.7

What is claimed is:
 1. A dental composition, wherein said composition comprises, on a surface of a dental substrate, a bonding agent; and a paste mixture, wherein the paste mixture was formed by mixing together a previously separated first part and a second part, and wherein the first part comprises at least one polymerizable monomer, a copper (II) compound, and at least one hydroperoxide, wherein said hydroperoxide is a tertiary hydroperoxide; and the second part comprises at least one thiourea compound, wherein said thiourea is selected from the group consisting of 1-(2-Pyridyl)-2-thiourea (PTU), 1-Benzoyl-2-thiourea (BTU), 1-Acetyl-2-thiourea (ATU), 1-(2-Tetrahydrofurfuryl)-2-thiourea (TTU), or a combination thereof; and wherein the bonding agent comprises 8% to 16% of at least one phosphoric acid containing (meth)acrylic monomer), wherein said phosphoric acid containing (meth)acrylic monomer is selected from the group consisting of GPDM (glycerol phosphate di(meth)acrylate{(meth)acrylate=acrylate or methacrylate}), phenyl-P (phenyl methacryloxyethyl phosphate), PENTA-P (dipentaerithritol pentaacrylate phosphate), 10-MDP (methacryloyloxydecyl phosphate), HEMA-P (hydroxyethylmethacrylate phosphate), HEA-P (hydroxyethylacrylate phosphate), bis(HEMA)-P {bis(hydroxyethylmethacrylate) phosphate), bis(HEA)-P {bis(hydroxyethylacrylate) phosphate), bis((meth)acryloxypropyl)phosphate, and combinations thereof.
 2. The dental composition of claim 1, wherein bond strength of the dental bonding agent on a dental substrate is more than 15 MPa.
 3. The dental composition of claim 1, wherein the hydroperoxide is Cumene hydroperoxide (CHP).
 4. The dental composition of claim 1, wherein the thiourea is 1-(2-Pyridyl)-2-thiourea (PTU).
 5. The dental composition of claim 1, wherein said phosphoric acid containing (meth)acrylic monomer is 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP).
 6. The dental composition of claim 1, wherein the dental substrate is Zirconia.
 7. The dental composition of claim 1, wherein the bonding agent is a single bottle bonding agent.
 8. A method of dental restoration, wherein said method comprises: a first step of applying a dental bonding agent on a dental substrate, wherein the bonding agent comprises at least one phosphoric acid containing (meth)acrylic monomer, wherein said phosphoric acid containing (meth)acrylic monomer is selected from the group consisting of GPDM (glycerol phosphate di(meth)acrylate{(meth)acrylate=acrylate or methacrylate }), phenyl-P (phenyl methacryloxyethyl phosphate), PENTA-P (dipentaerithritol pentaacrylate phosphate), 10-MDP (methacryloyloxydecyl phosphate), HEMA-P (hydroxyethylmethacrylate phosphate), HEA-P (hydroxyethylacrylate phosphate), bis(HEMA)-P {bis(hydroxyethylmethacrylate) phosphate), bis(HEA)-P {bis(hydroxyethylacrylate) phosphate), bis((meth)acryloxypropyl)phosphate, and combinations thereof; and a second step of applying paste mixture from a device having a first part and a second part separate from each other, wherein said first part and second part form the paste mixture, and wherein the paste mixture from the device comprises at least one polymerizable monomer a copper (II) compound, and at least one hydroperoxide in the first part, wherein said hydroperoxide is a tertiary hydroperoxide; and at least one thiourea compound in the second part, wherein said thiourea is selected from the group consisting of 1-(2-Pyridyl)-2-thiourea (PTU), 1-Benzoyl-2-thiourea (BTU), 1-Acetyl-2-thiourea (ATU), 1-(2-Tetrahydrofurfuryl)-2-thiourea (TTU), or a combination thereof, wherein either the first part or second part of the paste mixture further comprises a copper (II) compound, and wherein bond strength of the dental bonding agent on a dental substrate is more than 15 MPa.
 9. The dental composition of claim 1, wherein either the first part or second part of the paste mixture further comprises a copper (II) compound; wherein bond strength of the dental bonding agent on a dental substrate is more than 15 MP; wherein the hydroperoxide is Cumene hydroperoxide (CHP); wherein the thiourea is 1-(2-Pyridyl)-2-thiourea (PTU); and wherein said phosphoric acid containing (meth)acrylic monomer is 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP).
 10. The method of claim 8, wherein the bonding agent bonds effectively on a dental substrate.
 11. The method of claim 8, wherein the dental substrate is Zirconia.
 12. The method of claim 8, wherein the device is a dual-barrel syringe.
 13. The dental composition of claim 1, wherein the previously separated first part and a second part were separated in a dual-barrel syringe. 